A Long-Term Perspective of FAS.

Few people in their adolescent or adult years are diagnosed as having FAS. Studies have shown that most FAS patients outgrow the characteristic FAS facies after puberty. However, they may still suffer from mental handicaps and have poor age-appropriate life skills. Further research is needed to understand these patients' unique needs and to develop the most effective intervention strategies.

I n the 20 years since fetal alcohol syndrome (FAS) was identified as a birth defect, relatively few studies have described adolescents and adults with this disability, although FAS is thought to be the leading known cause of mental retardation. Many practical problems exist in accruing a population of adolescent and adult patients with FAS and in following them systematically past childhood. Yet by examining the natural history of FAS, it should be possible to evaluate the long term needs of these patients and to develop an appropriate set of lifetime interven tions suitable to their disabilities.
Taking a historical perspective, this article reviews the pertinent literature, describing the findings of several long term followup studies of children with FAS. It raises questions about the needs of adolescents and adults with FAS that should be addressed through future re search and public policy.

FAS: THE INITIAL RESEARCH
FAS is growing up. It is now 20 years since  coined the term "fetal alcohol syndrome" to describe children who had a specific and visually recognizable pattern of characteristics, and in July 1993, the first baby in the world to receive a diagnosis of FAS at birth celebrated his 20th birthday (figure 1). Children with similar characteristics had been independently identified in France (Lemoine et al. 1968) and in Seattle ) as a specific subgroup of children born to alcoholic mothers.
The characteristics of FAS were iden tified as growth deficiency; specific phys ical anomalies, including a characteristic facies (figure 2); and central nervous system (CNS) dysfunction. The CNS manifestations include delayed develop ment, hyperactivity, motor incoordina tion, learning or attentional problems, seizures, mental retardation, and/or mi crocephaly (small head). These early insights on FAS suggested a biological cause for some of the problems seen in children of alcoholic 1 mothers-and indicated that these problems could be prevented if women did not drink alcohol during pregnancy.
Two decades of laboratory research have validated these early findings on the 1 The term "alcoholic" has been defined in many ways. Here the term includes "alcohol abuse" and/or binge consumption but does not necessarily imply dependence. causes of FAS. For example, experimental research has shown that alcohol is terato genic 2 across a wide variety of species and conditions of exposure, and it is the most commonly used known human teratogen in the world. Alcohol also causes FAS, with an estimated prevalence of 1-3/1,000 live births (National Institute on Alcohol Abuse and Alcoholism 1990).

Early Research and Prevention Efforts
The early clinical reports of FAS by Lemoine and colleagues (1968) in west ern France and Jones and colleagues (1973) in Seattle were soon replicated by reports by Majewski and colleagues (1976) in western Germany, by Dehaene and colleagues (1977a) in northern France, and by Olegård and colleagues (1979) in Sweden. Like the initial reports, all of these studies in the 1970's described patients with FAS who were infants and young children. Because these children with FAS were mostly functioning within the borderline and retarded range of intel lectual development, FAS soon became FPO FAS: A LongTerm Perspective recognized as one of the three most preva lent causes of mental retardation with a known etiology-and the only one that was entirely preventable.
This knowledge stimulated the devel opment of important programs in the late 1970's, designed to demonstrate methods to prevent FAS and to intervene in mater nal alcohol abuse during pregnancy (Rosett et al. 1980;Rosett and Weiner 1981;Little and Streissguth 1981;Little et al. 1984Little et al. , 1985. The United States Government initiated two important policies: an offi cial government warning by the Surgeon General against drinking alcoholic bever ages during pregnancy or when planning a pregnancy (Public Health Service 1981), and the labeling of alcoholic beverage containers with a warning about the risk of birth defects associated with drinking alcohol during pregnancy (Public Law 100-690, 1988). It is impossible to know how many children were helped as a result of these official policies, but it is probably a large number. Research projects such as those by Little and colleagues (1984), Rosett and colleagues (1980), and Larsson and colleagues (1985) have clearly dem onstrated that curtailing alcohol use during pregnancy does improve pregnan cy outcome.
Initially, researchers thought that the CNS effects of FAS were primarily mani fested as mental retardation or microcephaly. There was an implicit assumption that the treatment and service needs of patients with FAS would be like those of patients with Down syndrome. (As a result of decades of research, a network of support services and special cradletograve pro grams exists nationwide to accommodate the special needs of Down syndrome patients.) However, FAS did not turn out to be like Down syndrome. Children with FAS manifest a wide range of intellectual abilities, and no early biological marker has yet appeared to help identify those at The first patient in whom FAS was diagnosed at birth at 8 and 18 years of age (also see figure 3A).  risk. Clinicians who continued to work with patients with FAS as they grew up realized that they often behaved very differently than patients with Down syn drome, often getting into trouble in their communities, in their schools, and with their families. This awareness led us to the next set of research studies.

ADOLESCENT MANIFESTATIONS OF FAS
As early as the mid1970's, Smith made the diagnosis of FAS in two young men who were examined for the first time as adults; both were mentally retarded. Their facial photographs and IQ profiles were published in 1978 (Clarren and Smith 1978;Streissguth et al. 1978). In 1981, Iosub and colleagues described longitudi nal data on three siblings with FAS who had been diagnosed in childhood. The two who had reached maturity had small heads, short palpebral fissures (eye openings), borderline to mild mental retardation, but variable growth deficiency; one was growth deficient only for height, the other only for weight.
During the first decade of FAS re search, most clinicians seemed reluctant to make the initial diagnosis in adoles cents and adults. This was understand able, as all the early patients identified were young children; the classic FAS face was the face of a young child (figure 2). Only patients with the most classic mani festations of FAS were identified initially as adolescents and adults. It was only when we were able to present systematic longitudinal data on the first children with a diagnosis of FAS that we were able to see how the physical features (the primary markers for the syndrome) changed with age, which makes initial identification more difficult in older patients. This first longterm FAS followup study ) was a 10year followup of the 11 children identified in Seattle in 1973. It revealed that the facial morphology of many persons with FAS changed as they matured. Longer noses and bigger chins often gave their faces a coarser look after puberty, a finding that has been confirmed by several other studies (Spohr et al. 1987Lemoine and Lemoine 1992;Majewski 1993). Girls in particular tend ed to put on weight at this time, and their weighttoheight age ratio changed from low to high.
Does this mean that FAS attenuates in adolescents? Absolutely not. The decreasing specificity of the face and the growth deficiency after puberty only explains why initial identification of people with FAS after puberty can be more difficult. In FAS, the physical fea tures are only the markers for the CNS deficits. As many studies of alcohol ter atogenesis have demonstrated, the brain is

e d b a s e d o n t h e f a c t t h a t m a n y p a t i e n t s w i t h F A S a r e m e n t a l l y r e t a r d e d . W e p u b l i s h e d t h e f i r s t m a j o r d a t a b a s e d s t u d y o f t h e l o n g t e r m c o n s e q u e n c e s o f F A S i n a d o l e s
c e n t s a n d a d u l t s i n 1 9 9 1 ( S t r e i s s g u t h e t a l . 1 9 9 1 a) . T h i s s t u d y , w h i c h i n v o l v e d 6 1 p a t i e n t s w h o r a n g e d i n a g e f r o m 1 2 t o 4 0 ( m e a n a g e 1 7 y e a r s ) ,

A FPO FPO FPO FPO
The first patient to be given the diagnosis of FAS at birth as a newborn and at ages 5, 10, and 14 years. He has been growth deficient and microcephalic throughout his life. As he has aged, his nose has shown considerable relative growth, resulting in a high, wide nasal bridge. His philtrum 1 has remained smooth. SOURCE: Streissguth et al. 1991a.

FPO FPO FPO FPO
Adolescent girl whose condition was diagnosed as FAS at birth, with later intellectual functioning in the borderline range, as a newborn, at 9 months, and at 5 and 14 years of age. Although her facial features are gradually maturing, she still has small palpebral fissures; a relatively long, smooth philtrum; and a narrow upper lip. SOURCE: Streissguth et al. 1991a.

FPO FPO FPO FPO
Woman whose condition was diagnosed as FAS at 4 years of age; she now has an IQ level of 85 to 90. Photographs show her at 9, 13, and 19 years. Her early FAS facial manifestations have evolved into a fairly normal facial phenotype by adult life. At 19, her head circumference was below the 1st percentile, her height was below the 5th percentile, and her weight was around the 10th percentile. SOURCE: Streissguth et al. 1991a.

LongTerm FAS Followup Studies From Europe
Re p o r t s fr o m th r e e si t e s in Ge r m a n y an d on e in Fr a n c e ha v e in ge n e r a l co n f i r m e d th e fi n d i n g s of th e Se a t t l e st u d i e s . Th e lo n g te r m me n t a l an d be h a v i o r a l co n s e qu e n c e s of FA S ar e se r i o u s , ye t th e pa t i e n t s ar e mo r e di f f i c u l t to re c o g n i z e fr o m th e i r ph y s i c a l ch a r a c t e r i s t i c s as th e y ma t u r e . I n 1 9 9 2 , L e m o i n e a n d L e m o i n e p u b l i s h e d a n i m p o r t a n t s t u d y  incontinence) and eating disorders declined greatly, whereas speech disorders, emo tional disorders, and unusual habits and stereotypic behaviors doubled in magni tude, characterizing approximately 45 to 50 percent of the sample.

p e r c e n t o f t h e s e p a t i e n t s h a d p h y s i c a l m a l f o r m a t i o n s ) . L e m o i n e f o u n d t h a t s e v e r i t y o f d i a g n o s i s w a s r e l a t e d t o c a u s e o f d e a t h i n p a t i e n t s w i t h F A S . A m o n g t h e 5 0 p a t i e n t s w i t h s e v e r e F
Although unusual habits and stereo typic behaviors decreased by the late school years, emotional disorders, fol lowed by hyperkinetic disorders, remained present in more than 50 percent of the 33 patients examined at both early and late school years. Conduct disorders remained constant in this group, at around 20 per cent. Data from the Achenbach scales revealed attentiondeficit problems as the most frequent problem, followed by social relationship problems, with the same pattern manifest at both examina tions during the school age period. Both parent and teacher Achenbach scales revealed attentional and social problems to be the most prominent peaks in the symptom profiles. Although boys tended to have higher psychopathology scores than girls, there was little difference in the type of symptoms manifested in children with FAS within these age ranges.

FUTURE DIRECTIONS FOR FAS RESEARCH
In the past few years, longterm followup studies of patients with FAS have been leading the field in a new direction. No longer can FAS be viewed as just a child hood disability-the changing needs of this population must be considered as they enter the adolescent years, which will (often for the first time) most clearly differentiate them from their peers. It is in early adolescence that many persons with FAS (even prior to a diagnosis) begin to express the feeling that they do not "think quite like everybody else." It is at this age that parents may begin to realize that "just trying harder" is not the whole solution.
No longer can FAS be viewed as just another type of mental retardation. Not only are there many patients with FAS whose intellectual abilities fall well with in the normal range, but they also are displaying an increasing and unsettling degree of recognizable psychopathology. Questions remain about the specific etiol ogy of the psychopathology and behav ioral disorders. Although it is always tempting to attribute psychopathology to adverse environments-and children with FAS have a greater likelihood of some adversity in their backgrounds-most followup studies of patients with FAS find a weaker than expected relationship.
Clinicians continue to see some pa tients with FAS who have severe cogni tive deficits lasting into adulthood but who have not had adverse rearing envi ronments. Clinicians also continue to see extremely variable outcomes in terms of secondary psychopathology and second ary disabilities that are not easily account ed for by either the level of the patients' overall intellectual ability or the status of their rearing environment. These unset tling discrepancies demonstrate the need for more research: research on the affect ed patients themselves, research on their genetic predispositions, and research on effective ways to modify and improve behavioral outcome in individual patients.
A recent report of differential out comes in dizygotic twins (fraternal twins) of alcoholic mothers should stimulate further investigation of the interaction of

No longer
can FAS be viewed as just a childhood disabilitythe changing needs of this population must be considered as they enter the adolescent years.
genetic and teratogenic influences on development (see Streissguth and Dehaene 1993). The almost complete absence of any literature on scientifically based interventions (either pharmacological or behavioral) should prompt researchers to study effective interventions for patients with FAS. It is hoped that the curious oversight by which FAS is not systemati cally addressed in the literature on chil dren of alcoholics will be resolved so that more studies will focus (as Werner [1986] has done) on individual differences in children of alcoholic mothers and children of alcoholic fathers. Documentation of prenatal alcohol exposure history should be a necessity in all studies of children of alcoholics, be cause both shortterm (Day 1992) and longterm ) conse quences of prenatal alcohol exposure per se, even in the absence of maternal alco holism or alcohol problems, has been reported from several cohort studies. Understanding the specific types of neu ropsychological deficits that underlie FAS psychopathology will be an important challenge for the future, as will the com plex interactions between individual levels of cognitive deficit and adverse and therapeutic environments.
The clinical work of the past 20 years also has suggested that what were thought to be suitable environmental interventions and educational opportunities for popula tions of retarded children (such as those with Down syndrome), are often not effective for patients with FAS. In partic ular, existing treatment and rehabilitative strategies seem less effective for people with FAS who are not classifiable as men tally retarded and for those whose mild cognitive deficits are compounded by attentional deficits or emotional instability.
Understanding the specific characteris tics and needs of patients with FAS/FAE will permit development of the most ap propriate interventions. Ideally such stud ies will not focus just on the preschool years and on academic attainment but will take a lifespan approach, with the goal of developing productive citizens who are capable of contributing to society at their own level of endowment. Recognizing the individual and specific needs of groups of patients with different types and etiolo gies of disabilities is an important current focus in developmental disabilities re search (see Burack et al. 1988;Dykens 1991, 1992). This approach is needed for patients with FAS, who often have multidisciplinary problems that in volve the home, the schools, the health care system, vocational training, the crimi nal justice system, and the community.
More and more, the behavioral charac teristics of FAS appear broad and diverse rather than tightly constrained around a narrow cognitive dimension. Although some overlap between FAS and existing psychiatric nomenclature has been ob served (see Shaywitz et al. 1980;Nanson 1992 and Nanson and Hiscock 1990 on attention deficits and childhood autism), FAS seems to have been largely ignored both in the psychiatric literature and in the psychiatric clinics in the United States. Steinhausen is the only psychia trist who has published continuing fol lowup studies (e.g., Steinhausen et al. 1993Steinhausen et al. , 1994) that assess specific psycho pathologic outcomes in patients with FAS. The recent study by Lemoine and Lemoine (1992) demonstrates the need for understanding prenatal alcohol expo sure and FAS as a potential cause of psychiatric disability.
Diagnostic issues in the field are far from resolved. Not only does the diagno sis of FAS include recognizing a wide range of individual capabilities and dif ferences, but there also are many fetal alcoholaffected children whose condition is not diagnosable because of the absence of specific facial characteristics. Without a diagnosis, such individuals often cannot receive the services they require.
As experimental animal studies ac crue, an increasing body of research demonstrates both the early and the life long behavioral effects of alcohol in offspring who are neither growth deficient nor malformed (see Goodlett and West 1992;Riley 1990;Means et al. 1989; see the article by Becker et al., pp. 10-16). Even prospective longitudinal human cohort studies are showing a variety of behavioral problems at lower doses of alcohol than are necessary to produce physical effects (Day 1992;. Further studies that emphasize the behavioral characteristics of alcohol teratogenesis are needed. By and large, it is the behavior and not the growth defi ciency or anomalies that present the primary problems to the patients them selves, their families, and society.
The body of research reviewed here, all generated during the past 20 years about a developmental disability that previously had been unknown, is exten sive. The research did not lead in the direction initially anticipated when FAS was first identified. Patients with FAS are not all mentally retarded, and their behav ioral problems are often more debilitating than their cognitive deficits would suggest.

EPILOG
One year ago I gave a public lecture on FAS. Seventy people attended. Afterward, three came up spontaneously to tell me their stories. Although the diagnostic speculations of these observers could not be confirmed, they illustrate the diverse faces of alcohol embryopathy that profes sionals see regularly in clinics serving patients with FAS/FAE. They also demon strate the apparent relevance of the re search on FAS to the individuals and families coping with related problems.
The first woman said, "My younger sister has FAS. I can tell from your pic tures and she's mentally retarded. I don't have FAS," she said, "I don't look like those pictures and I'm not mentally re tarded." "But," she told me, "I must have FAE. I've never been able to think like other kids and school was always very hard. My adoptive family had lots of testing done and sent me to psychiatrists, but they never figured out what was wrong with me. I just found out that my birth mother was an alcoholic. Now I'm 21, working on my GED, living on public assistance with my baby daughter-I still can't figure things out. I don't even know how to care for my daughter. Can you help me?" A man who approached me said his brotherinlaw had FAE. He said his wife was the protective payee for her brother, who simply couldn't manage his own affairs. Although the brother had attend ed school to become a chef, he couldn't work as a chef; instead he is a kitchen aide, a job he is comfortable with due to its predictability and repetitive nature. He is surviving marginally in the community except when he drinks. His mother, who had a graduate degree and worked as a professional in the community, had had a serious drinking problem during the preg nancy with this young man but not during the pregnancy with her daughter. Now as adults, the daughter cares for the son.
Finally, a sparkling 16yearold girl spoke. "I've always been bright and a good learner and loved school," she said, "but my mother has fetal alcohol syn drome. She looks just like those pictures and she's quite unable to function as an adult. She's always being victimized by men and really can't take care of herself. She couldn't take care of me either, that's why I was adopted. I only found her recently. The thing I'm really thankful for," she said, "is that she didn't drink during her pregnancy with me." ■